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Assessment of a Large-Scale Unbiased Malignant Pleural Effusion Proteomics Study of a Real-Life Cohort

dc.contributor.authorZahedi, S
dc.contributor.authorCarvalho, AS
dc.contributor.authorEjtehadifar, M
dc.contributor.authorBeck, HC
dc.contributor.authorRei, N
dc.contributor.authorLuís, A
dc.contributor.authorBorralho, P
dc.contributor.authorBugalho, A
dc.contributor.authorMatthiesen, R
dc.date.accessioned2022-09-19T20:37:55Z
dc.date.available2022-09-19T20:37:55Z
dc.date.issued2022
dc.description.abstractBackground: Pleural effusion (PE) is common in advanced-stage lung cancer patients and is related to poor prognosis. Identification of cancer cells is the standard method for the diagnosis of a malignant PE (MPE). However, it only has moderate sensitivity. Thus, more sensitive diagnostic tools are urgently needed. Methods: The present study aimed to discover potential protein targets to distinguish malignant pleural effusion (MPE) from other non-malignant pathologies. We have collected PE from 97 patients to explore PE proteomes by applying state-of-the-art liquid chromatography-mass spectrometry (LC-MS) to identify potential biomarkers that correlate with immunohistochemistry assessment of tumor biopsy or with survival data. Functional analyses were performed to elucidate functional differences in PE proteins in malignant and benign samples. Results were integrated into a clinical risk prediction model to identify likely malignant cases. Sensitivity, specificity, and negative predictive value were calculated. Results: In total, 1689 individual proteins were identified by MS-based proteomics analysis of the 97 PE samples, of which 35 were diagnosed as malignant. A comparison between MPE and benign PE (BPE) identified 58 differential regulated proteins after correction of the p-values for multiple testing. Furthermore, functional analysis revealed an up-regulation of matrix intermediate filaments and cellular movement-related proteins. Additionally, gene ontology analysis identified the involvement of metabolic pathways such as glycolysis/gluconeogenesis, pyruvate metabolism and cysteine and methionine metabolism. Conclusion: This study demonstrated a partial least squares regression model with an area under the curve of 98 and an accuracy of 0.92 when evaluated on the holdout test data set. Furthermore, highly significant survival markers were identified (e.g., PSME1 with a log-rank of 1.68 × 10−6 ).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCancers. 2022; 14: 4366.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.26/41831
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationStrategic Project - UI 100 - 2013-2014
dc.subjectMarcadores Tumoraispt_PT
dc.subjectDerrame Pleuralpt_PT
dc.subjectNeoplasias do Pulmãopt_PT
dc.subjectBiomarkers, Tumorpt_PT
dc.subjectPleural Effusionpt_PT
dc.subjectLung Neoplasmspt_PT
dc.titleAssessment of a Large-Scale Unbiased Malignant Pleural Effusion Proteomics Study of a Real-Life Cohortpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleStrategic Project - UI 100 - 2013-2014
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FQUI%2FUI0100%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBTM-TEC%2F30088%2F2017/PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream9471 - RIDTI
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication5d3dcf11-e867-464a-99fd-24195719b453
relation.isProjectOfPublicationec3893f4-5a54-480f-bed7-8d175f7b2601
relation.isProjectOfPublication.latestForDiscovery5d3dcf11-e867-464a-99fd-24195719b453

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